Researchers have found that a diet rich in fish, seafood, and grains - also called polyunsaturated fats - is better at preventing heart disease than a diet containing olive oil, nuts, and avocados - called monounsaturated fats. Although both types of fats are healthy, people should probably include more of the first than the second in their diet to keep a healthy heart, the scientists say.

Too much cholesterol has long been linked to increasing risks of developing heart disease, but it has been less clear how the various dietary fats - saturated, monounsaturated and polyunsaturated - make people susceptible to the disease.

Lawrence L. Rudel and colleagues developed a method to determine the effects of the three types of dietary fats on acyl-coenzyme A, a key molecule involved in the metabolism of fatty acids. The scientists found that mice fed diets high in saturated and monounsaturated fat showed an increase in acyl-coenzyme A compared to mice fed a diet enriched in polyunsaturated fat. These results suggest that polyunsaturated fat is a more suitable replacement than monounsaturated fat for dietary saturated fat, the scientists concluded.

Scientists have shown that a build-up of cholesterol in cell organelles called lysosomes is related to a higher incidence of heart disease.

Atherosclerosis, a heart disease in which fat accumulates in arteries and blocks blood flow, is the leading cause of death in the Western World. One hallmark of the disease is the presence of cells called macrophage foam cells, in which cholesterol accumulates. Scientists are now trying to understand how cholesterol builds up in these cells, especially in cellular organelles called lysosomes that are known for degrading cholesterol.

W. Gray Jerome and colleagues noticed that when cholesterol accumulates in lysosomes, they become less acidic, which makes them less active. The lysosomes become unable to degrade all the cholesterol that comes in, and more cholesterol accumulates over time. These observations suggest that restoring the acidity of lysosomes may be a promising way to clear up arteries from cholesterol and to potentially prevent heart disease.

Scientists have shown that a protein involved in cholesterol metabolism may cause the accelerated onset of Alzheimer's Disease in individuals affected with Down Syndrome.

People with Down Syndrome - a genetic disorder due to the presence of an extra chromosome 21 - develop Alzheimer's disease (AD) earlier (mid- to late 30s) than the general population (mid- to late 70s). To understand why, scientists have studied genes from chromosome 21 that are also involved in AD. One of those genes has already been found: It produces a protein called amyloid precursor protein (APP) that helps create protein clusters that are the hallmark of AD.

Cheryl L. Wellington and colleagues have found another gene on chromosome 21 that produces a protein that regulates the amount of cholesterol present in a cell. The scientists showed that this protein influences the distribution and processing of APP and that it is present at high levels in the brains of Down Syndrome individuals. The new discovery may provide new ways to halt AD symptoms early in these individuals.

The following article is the last in a series of nine reviews on "lipid post-translational modification" or how lipids are added to proteins after they are produced in the cell. The other articles in the series appeared in previous issues of the journal.

All thematic review articles and can be accessed at: http://www.jlr.org/ (under "Thematic Reviews").

How Lipids Anchor Proteins on a Cell Membrane

Peter Orlean and Anant K. Menon describe how a lipid that helps proteins attach to cell membranes is made. The protein, called glycosylphosphatidylinositol (GPI), is important because people with defective GPI can develop seizures, have heart attacks, and acquire a hemolytic condition in which red blood cells are destroyed. Also, elevated levels of certain proteins involved in GPI anchoring have been linked to breast and bladder cancers.

GPI synthesis is initiated on the cytoplasmic side of the membrane of the endoplasmic reticulum (ER), then the resulting precursor molecule flips inside the ER, where further molecules are progressively added to it to form the complete GPI. The GPI is then linked to a protein, and the lipid-modified protein then leaves the ER for the cell membrane, where it is anchored on the outer side of the membrane via its GPI.

Orlean and Menon review the latest findings on GPI assembly in the ER, its transfer to a protein, and the changes made to GPI on its way to the cell membrane. They describe the enzymes and chemical reactions involved and highlight questions that need to be addressed, especially how GPI structure affects the proteins they carry with them and how the various components of the GPI anchoring machinery work together. Answering these questions would not only help better understand GPI assembly, but could also lead to new drugs against diseases associated with defective GPI.

The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.

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